Abstract
Endometriosis is a chronic gynecologic disease that negatively affects the quality of life of many women. Unfortunately, endometriosis does not have a cure. The current medical treatments involve hormonal manipulation with unwanted side effects and high recurrence rates after stopping the medication. Sadly, a definitive diagnosis for endometriosis requires invasive surgical procedures, with the risk of complications, additional surgeries in the future, and a high rate of recurrence. Both improved therapies and noninvasive diagnostic tests are needed. The unique molecular features of endometriosis have been studied at the coding gene level. While the molecular components of endometriosis at the small RNA level have been studied extensively, other noncoding RNAs, such as long intergenic noncoding RNAs and the more recently discovered subset of long noncoding RNAs called circular RNAs, have been studied more limitedly. This review describes the molecular formation of long noncoding and the unique circumstances of the formation of circular long noncoding RNAs, their expression and function in endometriosis, and promising preclinical studies. Continued translational research on long noncoding RNAs, including the more stable circular long noncoding RNAs, may lead to improved therapeutic and diagnostic opportunities.
Highlights
Endometriosis is a progressive and debilitating gynecologic disease whereby endometriallike tissue grows outside the uterine cavity, invading adjacent organs, such as the ovaries, bladder, colon, or pelvic peritoneum [1,2,3]
The prevalence of endometriosis ranges from 5 to 15% of reproductive age women depending on the method of disease confirmation [3,6], affecting approximately 190 million women worldwide and 5 million women and adolescent girls in the United States [2]
Many deep sequencing studies on endometriosis have listed long noncoding RNAs (lncRNAs), including circRNAs, within the differentially expressed transcripts, but most of the manuscripts focus on proteincoding genes
Summary
Endometriosis is a progressive and debilitating gynecologic disease whereby endometriallike tissue grows outside the uterine cavity, invading adjacent organs, such as the ovaries, bladder, colon, or pelvic peritoneum [1,2,3]. Hormonal therapies, including gonadotropin-releasing hormone agonists and newer antagonists, can be prescribed only for a short time because of undesirable side effects, including irregular menstrual bleeding, the development of menopausal symptoms, and the detrimental impact on bone density [7,9,12] Both medical and surgical therapies fail to prevent recurrence [2] as 20–50% of endometriosis recurs within five years of treatment [13]. Short ncRNAs, including the ~22 nucleotide long miRNAs, have emerged as critical post-transcriptional regulators of gene expression that are fundamental for many disease processes [16]. Intergenic lncRNAs (long intergenic noncoding RNAs or lincRNAs) are located between two protein-coding genes and transcribed in the same direction as those genes. LncRNAs can be nuclear, cytoplasmic, or both, and the subcellular localization determines its function [31,35]
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